Ubiquitin-Binding Enzyme E2 Promotes Ovarian Cancer Cell Migratory and Proliferative Activity by Regulating EMT Induction

Abstract

Background and Objective: Ubiquitin-binding enzyme E2 (UBE2E2) is a member of the human ubiquitin-binding enzyme family that has previously been shown to be closely linked to the onset of a range of cancer types. The functional importance of UBE2E2 in ovarian cancer, however, has yet to be established. Accordingly, this study was developed to explore the role of UBE2E2 as a regulator of ovarian cancer cell malignancy. Methods: Gene Expression Omnibus (GEO) datasets were initially used to identify differentially expressed genes related to patient prognosis, revealing UBE2E2 as a hub gene in this cancer type. Immunohistochemical staining was used to compare UBE2E2 protein levels in ovarian cancer and control tissues, while the role of this protein as a regulator of malignant activity was tested through cell counting kit-8 (CCK-8) (CK001-01, sunview, Shenzhen, China), wound healing, and Transwell assays. In addition, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to evaluate the expression of markers related to the epithelial-mesenchymal transition (EMT) process. Results: Significant UBE2E2 protein and mRNA overexpression was evident in ovarian tumors, and higher UBE2E2 mRNA levels were associated with a worse ovarian cancer patient prognosis. Knocking down UBE2E2 in ovarian tumor cells was sufficient to inhibit their proliferation, migration, and invasivity. This UBE2E2 silencing additionally enhanced E-cadherin protein and mRNA expression while promoting significant Vimentin, Twist1, N-cadherin, and Zeb1 downregulation. Conclusions: UBE2E2 can promote ovarian cancer development and progression through mechanisms potentially linked to EMT induction. As such, UBE2E2 may represent a promising target for therapeutic intervention in patients diagnosed with this debilitating malignancy.